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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3051-3057. Prepublished online as a Blood First Edition Paper on January 4, 2005; DOI 10.1182/blood-2004-07-2974. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2974v1 105/8/3051    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Miller, J. S. Articles by McGlave, P. B. Search for Related Content PubMed PubMed Citation Articles by Miller, J. S. Articles by McGlave, P. B. Related Collections Immunobiology Neoplasia Immunotherapy Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer Jeffrey S. Miller, Yvette Soignier, Angela Panoskaltsis-Mortari, Sarah A. McNearney, Gong H. Yun, Susan K. Fautsch, David McKenna, Chap Le, Todd E. Defor, Linda J. Burns, Paul J. Orchard, Bruce R. Blazar, John E. Wagner, Arne Slungaard, Daniel J. Weisdorf, Ian J. Okazaki, and Philip B. McGlave From the Divisions of Medical and Pediatric Hematology-Oncology and Transplantation, Transfusion Medicine, the Blood and Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis. We previously demonstrated that autologous natural killer (NK)–cell therapy after hematopoietic cell transplantation (HCT) is safe but does not provide an antitumor effect. We hypothesize that this is due to a lack of NK-cell inhibitory receptor mismatching with autologous tumor cells, which may be overcome by allogeneic NK-cell infusions. Here, we test haploidentical, related-donor NK-cell infusions in a nontransplantation setting to determine safety and in vivo NK-cell expansion. Two lower intensity outpatient immune suppressive regimens were tested: (1) low-dose cyclophosphamide and methylprednisolone and (2) fludarabine. A higher intensity inpatient regimen of high-dose cyclophosphamide and fludarabine (Hi-Cy/Flu) was tested in patients with poor-prognosis acute myeloid leukemia (AML). All patients received subcutaneous interleukin 2 (IL-2) after infusions. Patients who received lower intensity regimens showed transient persistence but no in vivo expansion of donor cells. In contrast, infusions after the more intense Hi-Cy/Flu resulted in a marked rise in endogenous IL-15, expansion of donor NK cells, and induction of complete hematologic remission in 5 of 19 poor-prognosis patients with AML. These findings suggest that haploidentical NK cells can persist and expand in vivo and may have a role in the treatment of selected malignancies used alone or as an adjunct to HCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: NK cell adoptive immunotherapy Andrea Velardi Blood 2005 105: 3006. [Full Text] [PDF] This article has been cited by other articles: M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. Schwarer Killer Ig-Like Receptor Ligand Mismatch Directs NK Cell Expansion In Vitro J. Immunol., October 1, 2009; 183(7): 4502 - 4508. [Abstract] [Full Text] [PDF] F. Romagne, P. Andre, P. Spee, S. Zahn, N. Anfossi, L. Gauthier, M. Capanni, L. Ruggeri, D. M. Benson Jr, B. 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Zanotti, E. Oldani, A. Grassi, T. Intermesoli, C. Mico, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia Haematologica, May 1, 2007; 92(5): 612 - 618. [Abstract] [Full Text] [PDF] L. Zamai, C. Ponti, P. Mirandola, G. Gobbi, S. Papa, L. Galeotti, L. Cocco, and M. Vitale NK Cells and Cancer J. Immunol., April 1, 2007; 178(7): 4011 - 4016. [Abstract] [Full Text] [PDF] M. Carlsten, N. K. Bjorkstrom, H. Norell, Y. Bryceson, T. van Hall, B. C. Baumann, M. Hanson, K. Schedvins, R. Kiessling, H.-G. Ljunggren, et al. DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells Cancer Res., February 1, 2007; 67(3): 1317 - 1325. [Abstract] [Full Text] [PDF] L. Markasz, G. Stuber, B. Vanherberghen, E. Flaberg, E. Olah, E. Carbone, S. Eksborg, E. Klein, H. Skribek, and L. 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